Discovery medicine最新文献

{"title":"Mutation Characteristics of Phenylalanine Hydroxylase Gene in Children with Phenylketonuria in Yinchuan City.","authors":"Xinyou Yu,&nbsp;Fang Liu,&nbsp;Bo Wei,&nbsp;Meijuan Li,&nbsp;Ruiping Lu,&nbsp;Lihua Pan","doi":"10.24976/Discov.Med.202335177.54","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.54","url":null,"abstract":"<p><strong>Background: </strong>Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder affecting phenylalanine (Phe) metabolism caused by mutations in the phenylalanine hydroxylase (<i>PAH</i>) gene. It has a complex phenotype with many variants and genotypes in various populations. This study sets out to analyze the screening results of children with phenylketonuria (PKU) in Yinchuan City and characterize the mutation variants of the <i>PAH</i> gene.</p><p><strong>Methods: </strong>Phenylketonuria screening results were retrospectively analyzed in 398,605 neonates (207,361 males and 191,244 females) born in different maternity hospitals in Yinchuan City between January 2017 and December 2021. Screening for genetic metabolic diseases was performed with parental consent at their own expense. A comprehensive diagnosis was performed by integrating tandem mass spectrometry (MS/MS) findings with clinical presentations. High-throughput sequencing (HTS) was used to detect genetic and metabolic disease-associated genes in children with PKU who were clinically diagnosed and voluntarily tested. The identified loci were validated through Sanger sequencing and parental verification.</p><p><strong>Results: </strong>Among the screened newborns, 45 (11.3/100,000) PKU cases were diagnosed. In the 38 cases that underwent self-financed <i>PAH</i> sequencing, 56 mutations were detected in 76 chromosomes, with an overall detection rate of 73.7%. All patients harbored mutant genes, and the 56 mutations detected identified represented 14 variants, including 8 missense mutations, 2 splicing mutations, 2 nonsense mutations, and 2 silent mutations. The mutations were primarily distributed in <i>exons 2</i>, <i>3</i>, <i>6</i>, <i>7</i>, <i>9</i>, <i>11</i>, and <i>intron 4</i>, with the highest frequency observed in <i>exon 7</i> (25 [44.7%]), followed by <i>exon 11</i> (15 [26.7%]). The most prevalent mutations were <i>exon 7</i>-p.R252W (10 [17.9%]) and <i>exon 7</i>-p.R261Q (8 [14.3%]).</p><p><strong>Conclusions: </strong>The <i>PAH</i> gene mutations in children with PKU in Yinchuan City are predominantly concentrated in <i>exons 6</i>, <i>7</i>, and <i>11</i>, with the highest detection rates observed for p.R252W and p.R261Q mutations.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 177","pages":"533-538"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Model for the Diagnosis of Benign/Malignant Complex Cystic and Solid Breast Nodules.","authors":"Han Liu,&nbsp;Chun-Jie Hou,&nbsp;Jing-Lan Tang,&nbsp;An-Ning Liu,&nbsp;Ke-Feng Lu,&nbsp;Ying Liu,&nbsp;Pei Du","doi":"10.24976/Discov.Med.202335176.23","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.23","url":null,"abstract":"<p><strong>Purpose: </strong>To develop an ultrasound predictive model to differentiate between benign and malignant complex cystic and solid nodules (C-SNs).</p><p><strong>Methods: </strong>A total of 211 patients with complex C-SNs rated as American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) category 4 or 5 on the ultrasound reports were included in the study, from June 2018-2021. Multivariate stepwise logistic regression analysis was used to establish a predictive model, based on clinical and ultrasound features. The diagnostic performance of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve.</p><p><strong>Results: </strong>A total of 109 breast nodules, including 74 benign nodules (67.89%) and 35 malignant nodules (32.11%), were detected by surgical pathology or puncture biopsy. Multivariate analysis showed that the blood flow (BF) of complex C-SNs (<i>p</i> = 0.03), cystic fluid transmission (<i>p</i> = 0.02), longitudinal diameter (<i>p</i> < 0.001), and age (<i>p</i> = 0.03) were independent risk factors for malignant complex cystic and solid breast nodules. The ultrasound model equation was Z=-12.14+2.24×X12+1.97×X20+0.40×X7+0.11×X0; M=ez1+ez (<i>M</i> is the malignancy score, <i>e</i> = 2.72). The area under the curve (AUC) was 0.89, which indicated good predictive utility for the model.</p><p><strong>Conclusions: </strong>A prediction model incorporating major risk factors can predict the malignant C-SNs with accuracy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"221-232"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Toll-like Receptor 4 Expression on Inflammatory Responses Related to Premature Membrane Rupture Induced by Lipopolysaccharide.","authors":"Jie Zi,&nbsp;Fang Wang,&nbsp;Zebin Liu,&nbsp;Yunxia Wang,&nbsp;Liying Qiu,&nbsp;Guosheng Zhu,&nbsp;Henghua Li","doi":"10.24976/Discov.Med.202335176.43","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.43","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the mechanism through which the expression of Toll-like receptor 4 (TLR4) influences the lipopolysaccharide (LPS)-induced inflammatory response, a condition that is associated with premature rupture of membranes (PROM).</p><p><strong>Methods: </strong>Human myeloid leukemia mononuclear cells (THP-1) were employed as the experimental model. These cells were treated with LPS and the TLR4 inhibitor CLI-095 and subsequently divided into three groups. A range of assays were utilized, including methyl thiazolyl tetrazole (MTT) assay, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) for measuring TLR4 and tumor necrosis factor α (TNF-α) mRNA levels, double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for assessing monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase 9 (MMP-9), as well as secretion levels of interleukin (IL)-6 and IL-1β. And western blotting was used to detect the expression of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) p65, which are components of the TLR4 downstream signaling pathway.</p><p><strong>Results: </strong>The LPS-induced proliferation of THP-1 cells was significantly inhibited (<i>p</i> < 0.05) when compared with normal THP-1 cells. Moreover, LPS also promoted TLR4 mRNA and protein expression levels, TNF-α mRNA expression, secretion of inflammatory factors, and phosphorylation of ERK and NF-κB p65 proteins (<i>p</i> < 0.05). On the other hand, administration of the TLR4 inhibitor CLI-095 significantly inhibited the expression of TLR4 mRNA and protein. It also effectively increased the proliferative activity of THP-1 cells and inhibited the secretion of TNF-α and inflammatory factors, as well as the phosphorylation of ERK and NF-κB p65 proteins (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>In summary, suppressing TLR4 expression can mitigate inflammatory responses, thereby reducing the likelihood of premature rupture of membranes during pregnancy, which is often triggered by such inflammation.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"429-435"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amonafide Induces HUVEC Senescence by Inhibiting Autophagy.","authors":"Jing Xia,&nbsp;Yu Zhou,&nbsp;Siyue He,&nbsp;Manoj Kumar Vashisth,&nbsp;Huijie Jia,&nbsp;Qianlong Dai,&nbsp;Yufen He,&nbsp;Xiaobo Wang","doi":"10.24976/Discov.Med.202335176.27","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.27","url":null,"abstract":"<p><strong>Background: </strong>Amonafide (Amo), due to hematotoxicity and digestive tract symptoms, the clinical application of which is limited. Several studies have reported that chemotherapy side effects are closely related to cellular senescence accumulation. Our study aims to examine whether amonafide causes senescence in human umbilical vein endothelial cell (HUVEC) lines and investigate its mechanisms associated with senescence.</p><p><strong>Methods: </strong>The experiments of expression of genes and proteins associated with aging were carried out with HUVEC cell lines. The experiments were divided into a control group and an amonafide group with different days. The HUVEC senescence cells were detected by SA-β-Gal staining, Western blotting detected the protein levels of p16, p53, AMPK (Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase), mTOR (mechanistic Target of Rapamycin), p62, and LC3 (microtubule-associated protein1 light chain 3, MAP1LC3). Fluorescence detected the expression of mRFP (monomeric Red Fluorescent Protein)-GFP (Green Fluorescent Protein)-LC3 and LC3 puncta of HUVEC cells. RT-qPCR (Real-Time Quantitative Polymerase Chain Reaction) tested the expressions of <i>p53</i>, <i>p21</i>, <i>IL</i> (Interleukin)<i>-1β</i>, <i>IL-6</i> (Interleukin-6), <i>IL-8</i> (Interleukin-8), and <i>MCP-1</i> (Monocyte Chemoattractant Protein-1). CCK-8 (Cell Counting Kit-8) assessed the HUVEC cell viability.</p><p><strong>Results: </strong>Here, we reported that amonafide resulted in an increased proportion of SA-β-Gal positive cells, high expression of aging-related proteins (p53 <i>p</i> < 0.05; p16 <i>p</i> < 0.05), and aging-related genes (<i>p53 p</i> < 0.05; <i>p21 p</i> < 0.05; <i>IL-1β p</i> < 0.05; <i>IL-6 p</i> < 0.05; <i>IL-8 p</i> < 0.05; <i>MCP-1 p</i> < 0.05) on the 3rd day. Mechanistically, amonafide could cause an increase in the levels of the mTOR (<i>p</i> < 0.05) on days 1 and 3, and p62 protein (<i>p</i> < 0.05) on day 1, and a decline in LC3II (microtubule-associated protein1 light chain 3Ⅱ)/LC3I levels (<i>p</i> < 0.05) on day 3, which is associated with the regulation of senescence. Additionally, the viability of HUVECs (human umbilical vein endothelial cells) was significantly inhibited by amonafide starting with a concentration of 0.8 μm (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>We first discovered that amonafide caused normal cellular senescence in our experiments. Amonafide-induced cellular aging by inhibiting autophagy and activating the mTOR pathway. The findings may offer new strategies for managing adverse reactions to amonafide.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"264-274"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXM1 Contributes to Chemotherapy Sensitivity in Cervical Cancer by Regulating TTK.","authors":"Qing Tang,&nbsp;Anli Xu,&nbsp;Ying Yang,&nbsp;Yunmei Zhang,&nbsp;Jianan Sun","doi":"10.24976/Discov.Med.202335176.22","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.22","url":null,"abstract":"<p><strong>Background: </strong>The emergence of chemotherapy resistance usually causes therapeutic failure in advanced cervical cancer. Forkhead box protein M1 (FOXM1) and threonine tyrosine kinase (TTK) are closely associated with cancer drug sensitivity, but the mechanism of FOXM1 on TTK involvement in chemo-treated cervical cancer remains unclear. Here, we aimed to observe the effects of FOXM1 on TTK and on chemotherapy sensitivity in cervical cancer.</p><p><strong>Methods: </strong>The expressions of FOXM1 and TTK in cervical cancer tissues and para-cancerous tissues were analyzed by immunohistochemistry. SiHa and Hela cells were transfected with human lentivirus-FOXM1, small interfering RNA (siRNA) or pcDNA3.1/FOXM1 to analyze the changes in TTK protein expression. Furthermore, the cells were treated with paclitaxel (8 μM) or cisplatin (10 μM) to analyze the effects of FOXM1 on chemotherapy sensitivity. SiHa cells were used to construct a xenograft model to study the effects of FOXM1 expression in response to paclitaxel treatment. The tumor size and weight were observed. The expressions of Ki-67, FOXM1, and TTK protein in tumor tissues were measured by immunohistochemistry.</p><p><strong>Results: </strong>High expression of FOXM1 and TTK were found in the cervical cancer tissues (<i>p</i> < 0.05). The TTK protein expressions were decreased by FOMX1-siRNA transfection in SiHa and Hela cells (<i>p</i> < 0.01). The cell viability and cell cycle were also suppressed by FOMX1-siRNA transfection (<i>p</i> < 0.01) but enhanced by pcDNA3.1/FOXM1 transfection (<i>p</i> < 0.01). For paclitaxel or cisplatin treatment, the cell viability and cell DNA damage were improved due to the FOXM1 overexpression (<i>p</i> < 0.01). TTK inhibitor significantly suppressed the effects of FOXM1 overexpression (<i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>FOXM1 regulated TTK and affected the therapeutic efficacy of cisplatin and paclitaxel in cervical cancer.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"208-220"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lumbar Extensor and Flexor Muscle Structural Changes in Young Female Nurses with Chronic Bilateral Non-Specific Low Back Pain: A Case-Control Study.","authors":"Wan-Ping Zhu,&nbsp;Yue Huang,&nbsp;Peng Hu,&nbsp;Wei Lin","doi":"10.24976/Discov.Med.202335176.45","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.45","url":null,"abstract":"<p><strong>Background: </strong>Muscle structural studies on non-specific low back pain in young female nurses are rare. This study aimed to investigate the changes of lumbar extensor and flexor muscle cross-sectional area and fatty infiltration in young female nurses with chronic bilateral non-specific low back pain by lumbar spine magnetic resonance imaging to speculate on the possible pathogenesis.</p><p><strong>Methods: </strong>The magnetic resonance imaging (MRI) data of 58 female nurses with chronic bilateral non-specific low back pain and 60 healthy female controls were analyzed retrospectively. The lumbar extensor and flexor muscle cross-sectional area/intervertebral disc cross-sectional area ratio, as well as magnetic resonance imaging signal intensity of lumbar extensor (erector spinae; multifidus) and flexor muscles (psoas muscle) were measured, calculated and compared between nurses and healthy controls by independent samples <i>t</i>-test. In addition, each mean MRI signal intensity of lumbar extensor or flexor muscles in nurses at different anatomical segments from lumbar vertebrae 2 (L2)-L3 to L5-sacral vertebrae 1 (S1) was also compared, and one-way Analysis of Variance (ANOVA) analyzed the mean MRI signal intensity between muscles in nurses with multiple comparisons.</p><p><strong>Results: </strong>There was no significant difference in lumbar extensor and flexor muscle cross-sectional area/intervertebral disc cross-sectional area ratio between nurses with chronic bilateral non-specific low back pain and healthy controls, <i>p</i> > 0.01. The magnetic resonance imaging signal intensity in lumbar extensor and flexor muscle was significantly higher in nurses with chronic bilateral non-specific low back pain than in healthy controls, <i>p</i> < 0.01. The MRI signal intensity of lumbar extensor muscle at the lower lumbar segments was higher than at the upper ones. The magnetic resonance imaging signal intensity of the extensor muscle (erector spinae; multifidus) was significantly higher than that of the flexor muscle (psoas muscle), <i>p</i> < 0.01.</p><p><strong>Conclusions: </strong>This study showed that young nurses with chronic bilateral non-specific low back pain have lumbar extensor and flexor muscle fatty infiltration without muscle atrophy. We hypothesized that muscle fatty infiltration may occur prior to muscle atrophy. Therefore, the high fatty infiltration of the lumbar extensor and flexor muscle may be a cause or a result of chronic bilateral non-specific low back pain in young nurses.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"444-450"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Increases Radiosensitivity of Radioresistant Nasopharyngeal Cancer.","authors":"Guoyu Wang,&nbsp;Jie Zhu,&nbsp;Zengxian Wang,&nbsp;Zuliang Xu,&nbsp;Yiming Shi,&nbsp;Lingjie Luo","doi":"10.24976/Discov.Med.202335176.42","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.42","url":null,"abstract":"<p><strong>Objectives: </strong>To study the effects of curcumin on the proliferation, invasion, apoptosis, and radiosensitivity of the radioresistant nasopharyngeal carcinoma (NPC) C6661-IR strain as well as the potential radiosensitization mechanism.</p><p><strong>Methods: </strong>NPC cells were continuously irradiated with different intensities of radiation to induce radiation-resistant cell lines. A plate clone formation assay was used to evaluate the effect of curcumin on the radiosensitivity of NPC cells. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was conducted to detect changes in cell viability. Flow cytometry was employed to analyze apoptosis percentage as well as Transwell® assay and immunofluorescence assay to observe cell invasion. Western blotting was applied to detect the expression levels of Bax, Bcl-2, and pro/cleaved-caspase 3. MiR-205-5p mimics and si-TP53INP1 were synthesized and transfected into C6661-IR cells, and the cells were then incubated with 10 μm/L curcumin. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to measure miR-205-5p levels and western blotting was conducted to detect the expression of TP53INP1.</p><p><strong>Results: </strong>The optimal radiation dose of X-ray was 6 Gy, and this dose was used in all subsequent experiments. Curcumin treatment significantly inhibited the proliferation and invasion of C6661-IR cells, promoted apoptosis and enhanced radiosensitivity. Compared to the 0 Gy+Cur group and the 6 Gy+Cur group, the miR-205-5p levels were higher in the C6661-IR cells of the 0 Gy and 6 Gy groups. Moreover, miR-204-5p was found to directly target TP53INP1. Curcumin downregulated miR-205-5p levels and upregulated TP53INP1 expression (<i>p</i> < 0.05). Thus, modulation of miR-205-5p or TP53INP1 expression attenuates the biological effects of curcumin on C6661-IR cells.</p><p><strong>Conclusions: </strong>Curcumin inhibited the proliferation and invasion of C6661-IR, promoted apoptosis, and enhanced its radiosensitivity to X-rays by mediating miR-205-5p/TP53INP1 expression.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"418-428"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FABP4 Regulates Cell Proliferation, Stemness, Apoptosis, and Glycolysis in Colorectal Cancer via Modulating ROS/ERK/mTOR Pathway.","authors":"Yingchao Gao,&nbsp;Yuanyuan Wang,&nbsp;Xin Wang,&nbsp;Jianwei Ma,&nbsp;Ming Wei,&nbsp;Na Li,&nbsp;Zengren Zhao","doi":"10.24976/Discov.Med.202335176.37","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.37","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is a common digestive tract malignancy. This study aimed to expound the functional role of fatty-acid-binding protein 4 (FABP4) and the potential underlying mechanisms in the development of colorectal cancer.</p><p><strong>Methods: </strong>Several techniques were utilized to investigate the role of FABP4 in colorectal cancer. FABP4 mRNA expression was quantified using Real time-quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), sphere formation assays and flow cytometry evaluated cell growth, stemness, and apoptosis in SW480 and HT29 cells. Glycolysis was assessed via extracellular acidification rate (ECAR) , lactate production, glucose uptake, adenosine triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio, and Glut1 and Elevated lactate dehydrogenase A (LDHA) protein expression. Reactive oxygen species (ROS) levels were analyzed by flow cytometry. Western blot measured the protein expression of FABP4, Proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, Glut1, LDHA, stemness makers (Sox2, Oct4, and ALDHA1), and extracellular regulated protein kinase (ERK)/mammalian target of rapamycin (mTOR) pathway proteins. <i>In vivo</i> experiments, BALB/c nude mice (n = 12) were inoculated with 200 μL HT29 cells (5 × 10⁶ cells) transfected with sh-FABP4 or short hairpin (sh)-negative control (NC), forming two groups with 6 mice each. The <i>in vivo</i> mice tumor model allowed for evaluating FABP4's impact on tumor growth.</p><p><strong>Results: </strong>FABP4 was significantly upregulated in colorectal cancer tissues and cells (<i>p</i> < 0.05). FABP4 knockdown markedly inhibited cell proliferation, stemness, and glycolysis, while promoting apoptosis in these cells (<i>p</i> < 0.05). Additionally, FABP4 depletion led to a significant increase in ROS level (<i>p</i> < 0.05). However, N-acetyl-L-cysteine (NAC) (<i>p</i> < 0.05), a ROS scavenger, mitigates these effects. Furthermore, the effects of FABP4 depletion on cell growth, stemness, glycolysis, and apoptosis in colorectal cancer cells were also retarded by NAC (<i>p</i> < 0.05). Notably, FABP4 knockdown also suppressed the ERK/mTOR pathway, suggesting its regulation via ROS (<i>p</i> < 0.05). <i>In vivo</i> study results showed, FABP4 depletion significantly curbed tumor growth in colorectal cancer (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>These results suggest that FABP4 depletion inhibits colorectal cancer progression by modulating cell growth, stemness, glycolysis and apoptosis. This regulation occurs through the ROS/ERK/mTOR pathway.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"361-371"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patching Retinal Breaks with Chitosan for Retinal Detachment in Rabbits.","authors":"Qingquan Wei,&nbsp;Yanyun Jiang","doi":"10.24976/Discov.Med.202335176.30","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.30","url":null,"abstract":"<p><strong>Background: </strong>Rhegmatogenous retinal detachment (RRD) is caused by one or more full-thickness retinal breaks. The current RRD treatments have several drawbacks. Chitosan is one of the most commonly used natural polymers for wound healing and has been demonstrated to be biodegradable, biocompatible, non-toxic, bioadhesive, and bioactive. This study aimed to determine the reliability and effectiveness of chitosan for sealing retinal breaks in rabbits.</p><p><strong>Methods: </strong>Eighteen blue purple rabbits were randomly divided into three groups: chitosan (n = 6), RRD (n = 6), and control (n = 6). The RRD model was established using vitrectomy, making retinal holes, and subretinal fluid injection in the RRD and chitosan groups. One week after the establishment of the model, chitosan was applied within the range of the holes in the chitosan group, and the vitreous body was filled with perfusion fluid. Except the chitosan treatment, the RRD group underwent the same procedure. Intraocular pressure (IOP) measurement, fundus photography, B-mode ultrasound, optical coherence tomography (OCT), histology, and enzyme linked immunosorbent assay (ELISA) were performed.</p><p><strong>Results: </strong>Retinas of all eyes in the RRD group were detached, whereas those of all eyes in the chitosan group remained attached. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF)-2, transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and IL-8 in the vitreous fluid of the RRD group were significantly higher than those of the control group (<i>p</i> < 0.05). Furthermore, the concentrations of EGF, FGF-2, TGF-β, and VEGF in the vitreous fluid of the chitosan group were higher compared to those of the RRD group (<i>p</i> < 0.05), whereas the concentrations of IL-6 and IL-8 were lower (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Chitosan may be a reliable method for sealing retinal breaks. Moreover, chitosan can maintain high levels of growth factors and reduce inflammatory factors in the vitreous, which may reduce and delay the death of retinal cells and help restore visual function after retinal repositioning.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"293-299"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Exploration of Osteosarcoma Metastasis Diagnostic Markers Based on Tumor-Associated Neutrophils.","authors":"Shan Tan,&nbsp;Rui Chao","doi":"10.24976/Discov.Med.202335176.31","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335176.31","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The high rate of the recurrence and metastasis of osteosarcoma (OS) is the major cause of its poor prognosis. There is a strong correlation between tumor-associated neutrophils (TANs) and tumor progression, progression, and metastasis. This study aimed to identify potential markers that could predict OS metastasis based on analysis of TANs in the tissues of OS patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A single-cell sequencing dataset (GSE152048), containing seven primary OS lesions, two recurrent OS lesions, and two lung metastatic OS lesions was used for TANs subset identification using the R software (version 4.1.0, R Project for Statistical Computing, Vienna, Austria; https://www.r-project.org/). Immune cell infiltration and immune score were analyzed using CIBERSORT algorithm and ESTIMATE database, respectively. The differentially expressed genes (DEGs) of TANs were used for weighted gene co-expression network analysis (WGCNA) to screen key genes associated with OS metastasis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were used to analyze the functions and signaling pathways involved in key genes. The mRNA levels of protein phosphatase 2 regulatory subunit B'gamma (&lt;i&gt;PPP2R5C&lt;/i&gt;) were validated in human osteosarcoma cell lines U2-OS and MG63, human normal cervical endometrial cell line HUCEC, and human foreskin fibroblast (HFF-1) cell line by real-time qPCR (RT-qPCR). &lt;i&gt;PPP2R5C&lt;/i&gt;-siRNA991 was transfected into U2-OS and MG63 for 48 h, then the expression levels of PPP2R5C, AKT serine/threonine kinase (&lt;i&gt;AKT&lt;/i&gt;), and phospho-AKT (p-AKT) were determined by RT-qPCR and Western blotting. Cell proliferation, migration, and apoptosis were measured by cell counting kit-8 (CCK-8), Transwell, and flow cytometry, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified TANs subsets in primary, metastatic, and recurrent OS. Immune infiltration analysis showed that TANs were expressed in OS. Compared with non-metastatic OS, metastatic OS had lower stromal score, immune score, ESTIMATE score, and higher tumor purity. WGCNA classified DEGs into five clusters, according to their function and identified &lt;i&gt;PPP2R5C&lt;/i&gt;, protein phosphatase 2 regulatory subunit B'epsilon (&lt;i&gt;PPP2R5E&lt;/i&gt;), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (&lt;i&gt;YWHAG&lt;/i&gt;) and CREB binding protein (&lt;i&gt;CREBBP&lt;/i&gt;), as potential markers that may affect TANs-induced OS metastasis via hypoxia inducible factor 1 (HIF-1), phosphatidylinositol 3-kinases (PI3K)-AKT and Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathways. &lt;i&gt;In vitro&lt;/i&gt; experiments demonstrated that the mRNA and protein expressions of &lt;i&gt;PPP2R5C&lt;/i&gt;, &lt;i&gt;PPP2R5E&lt;/i&gt;, &lt;i&gt;YWHAG&lt;/i&gt;, and &lt;i&gt;CREBBP&lt;/i&gt; were highly expressed in U2-OS and MG63 cells (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Furthermore, &lt;i&gt;PPP2R5C&lt;/i&gt; reduced proliferation and migration (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) and increased","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"35 176","pages":"300-311"},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}